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Nuria Bruguera-Avila,1–3 Alicia Marin,3–5 Ignasi Garcia-Olive,3–5 Joaquim Radua,6–8 Cristina Prat,4,9,10 Montserrat Gil,3 Juan Ruiz-Manzano2–5 1Department of Medicine, Hospital Sant Jaume de Calella, Calella, Barcelona, Spain; 2Department of Medicine, Universitat Autònoma de Barcelona, Bellatera, Spain; 3Department of Pulmonary Medicine, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet sn, Badalona, Barcelona, Spain; 4Ciber de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; 5Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Carretera del Canyet sn, Badalona, Barcelona, Spain; 6Department of Statistics, FIDMAG Germanes Hospitalaries Research Unit, Sant Boi de Llobregat, Barcelona, Spain; 7CiberSam – Ciber de Salud Mental, Madrid, Spain; 8Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 9Department of Microbiology, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet sn, Badalona, Barcelona, Spain; 10Department of Genetics and Microbiology of Universitat Autònoma de Barcelona, Bellatera, Spain Objectives: To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas aeruginosa (PA) is associated with a decrease of the number and duration of severe exacerbations.Materials and methods: Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010–December 2014) period were prospectively included. Repeated-measures t-tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalizations, comparing for each patient the year prior to the introduction of colistin with the year after.Results: After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (P=0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P=0.00005). These results persisted when patients with and without bronchiectasis or with and without persistence of Pseudomonas were separately analyzed. No pre–post differences were detected in the number of exacerbations not requiring admission.Conclusion: Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA. Clinical trials with a larger number of patients are needed in order to confirm these results. Keywords: bronchiectasis, colistin, COPD, nebulized antibiotics

Objective: To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. Methods: TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8–283.4); being retired (HR = 2.4;CI:1.1–5.1); having visited the emergency department (HR = 3.1;CI:1.2–7.7); HIV infection (HR = 3.4;CI:1.6–7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2–3.3) or non-standard treatments (HR = 2.68;CI:1.36–5.25); comprehension difficulties (HR = 2.8;CI:1.3–6.1); and smear-positive sputum (HR = 2.3-CI:1.0–4.8). Conclusion: There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs. [ABSTRACT FROM AUTHOR]

Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.

Study Objectives: To evaluate the diagnostic accuracy of a non-invasive technology based on image processing for the identification of obstructive sleep apnea (OSA) and its severity at patients' home., Methods: Observational, prospective, diagnostic accuracy study to evaluate the degree of measure agreement between Sleepwise (SW), in-laboratory attended polysomnography (PSG) and a home sleep apnea test (HSAT). 38 consecutive subjects with suspected OSA referred as outpatients to the sleep unit were recruited from September 2016 to September 2017. All patients underwent in-laboratory attended PSG and image processing with SW simultaneously overnight. Subsequently, a HSAT and image processing with SW were performed simultaneously overnight at patients' home, and the 2 nights after, patients underwent only image processing with SW consecutively., Results: In-laboratory polysomnography and SW had a Lin's concordance correlation coefficient of 0.933 and a κ of 0.930. Between HSAT and SW the Lin's concordance correlation coefficient was 0.842 and a κ of 0.571. Agreement between two consecutive nights with SW recording showed a Lin's concordance correlation coefficient of 0.923 and a κ of 0. 837., Conclusions: SW was highly accurate for non-invasive and automatic diagnosis of OSA in outpatients compared to standard methods for OSA diagnosis either in-laboratory attended PSG or HSAT. SW proved to be a technique with repeatable and concordant results on different nights for the same patient. We conclude SW is a non-invasive, easy-to-use, portable, effective and highly accurate system for the in-home diagnosis of OSA., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

Interferon gamma (IFN-γ) release assays (IGRAs) are increasingly used to test for latent tuberculosis (TB) infection. Although highly specific, IGRAs have a relatively high false-negative rate in active TB patients. A more sensitive assay is needed. IFN-γ-induced protein 10 (IP-10) is an alternative biomarker with a 100-fold-higher expression level than IFN-γ, allowing for different analysis platforms, including molecular detection. The PCR technique is already an integrated tool in most TB laboratories and, thus, an obvious platform to turn to. In this case-control study, we investigated the diagnostic sensitivity and specificity of a molecular assay detecting IP-10 mRNA expression following antigen stimulation of a blood sample. We included 89 TB patients and 99 healthy controls. Blood was drawn in QuantiFeron-TB gold in-tube (QFT) assay tubes. Eight hours poststimulation, IP-10 mRNA expression was analyzed, and 20 h poststimulation, IP-10 and IFN-γ protein plasma levels were analyzed using an in-house IP-10 enzyme-linked immunosorbent assay (ELISA) and the official QFT ELISA, respectively. The IP-10 mRNA assay provided high specificity (98%), sensitivity (80%), and area under the concentration-time curve (AUC) (0.97); however, the QFT assay provided a higher overall diagnostic potential, with specificity of 100%, sensitivity of 90%, and AUC of 0.99. The IP-10 protein assay performed on par with the QFT assay, with specificity of 98%, sensitivity of 87%, and AUC of 0.98. We have provided proof of high technical performance of a molecular assay detecting IP-10 mRNA expression. As a diagnostic tool, this assay would gain from further optimization, especially on the kinetics of IP-10 mRNA expression., (Copyright © 2020 American Society for Microbiology.)

Objective: The objective of the study was to determine the trend of variables related to tuberculosis (TB) from the Integrated Tuberculosis Research Program (PII-TB) registry of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), and to evaluate the PII-TB according to indicators related to its scientific objectives., Method: Cross-sectional, population-based, multicenter study of new TB cases prospectively registered in the PII-TB between 2006 and 2016. The time trend of quantitative variables was calculated using a lineal regression model, and qualitative variables using the χy test for lineal trend., Results: A total of 6,892 cases with an annual median of 531 were analyzed. Overall, a significant downward trend was observed in women, immigrants, prisoners, and patients initially treated with 3 drugs. Significant upward trends were observed in patients aged 40-50 and > 50 years, first visit conducted by a specialist, hospitalization, diagnostic delay, disseminated disease and single extrapulmonary location, culture(+), sensitivity testing performed, drug resistance, directly observed treatment, prolonged treatment, and death from another cause. The scientific objectives of the PII-TB that showed a significant upward trend were publications, which reached a maximum of 8 in 2016 with a total impact factor of 49,664, numbers of projects initiated annually, presentations at conferences, and theses., Conclusions: PII-TB provides relevant information on TB and its associated factors in Spain. A large team of researchers has been created; some scientific aspects of the registry were positive, while others could have been improved., (Copyright © 2019 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

New evidence and knowledge about the clinical management of drug-resistant tuberculosis (TB) in the last 3 years, makes it necessary to update the recent guideline published by SEPAR in 2017, mainly in relation to new diagnostic methods, drug classification, and regimens of treatment recommended to treat patients with isoniazid-resistance TB, rifampicin resistance TB and multidrug-resistant TB. With respect to tuberculosis diagnosis, we recommend the use of rapid molecular assays that also help to detect mutations associated with resistance. In relation to the treatment of multidrug-resistant TB we prioritize effective all-oral shorter treatment regimens including bedaquiline, a fluoroquinolone (levofloxacin or moxifloxacin), bedaquiline and linezolid, instead of the previously recommended short-course treatment with aminoglycosides and other less effective and more toxic drugs. The design of these regimens (initial schedule and changes in the regimen if necessary) should be made in accordance with drug-resistant TB experts; the treatment should be the responsibility of personnel with experience in the treatment of TB and in TB units guaranteeing the follow-up of the treatment and the management of drugs adverse effects., (Copyright © 2020 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction and Objective: Air pollution has been widely associated with respiratory diseases. Nevertheless, association between air pollution and exacerbations of asthma in our area has been less studied. To analyse the effect of air pollution on exacerbations of asthma in Badalona., Material and Methods: This was an observational study conducted in Badalona. The number of daily hospital admissions and accident and emergency visits related to exacerbation of asthma between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, atmospheric pressure, relative humidity, and NO 2 , SO 2 and CO levels on asthma-related emergencies and hospitalisations the same day and 1-4 days after. All p-values were corrected for multiple comparisons., Results: The number of hospitalisations was associated with low temperature (lags 0 to 4) and higher levels of NO 2 (lags 0, 1, 2 and 4) and atmospheric pressure (lags 2 and 3). The number of accident and emergency visits was associated with low temperature (lags 0 to 4) and higher levels of NO 2 (lags 2, 3 and 4)., Conclusions: The number of accident and emergency visits and hospitalisations for exacerbation of asthma is associated with higher levels of NO 2 and with lower temperatures., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

The immunological characterization of different cell markers has opened the possibility of considering them as immune tools for tuberculosis (TB) management, as they could correlate with TB latency/disease status and outcome. CD4 + T-cells producing IFN-γ + with a low expression of CD27 have been described as an active TB marker. In addition, there are unknown homing receptors related to TB, such as CCR4, which might be useful for understanding TB pathogenesis. The aim of our study is focused on the assessment of several T-cell subsets to understand immune-mechanisms in TB. This phenotypic immune characterization is based on the study of the specific immune responses of T-cells expressing CD27 and/or CCR4 homing markers. Subjects enrolled in the study were: (i) 22 adult patients with active TB, and (ii) 26 individuals with latent TB infection (LTBI). Blood samples were drawn from each patient. The expression of CD27 and/or CCR4 markers were analyzed within CD4 + T-cells producing: (i) IFN-γ + , (ii) TNF-α + , (iii) TNF-α + IFN-γ + , and (iv) IFN-γ + and/or TNF-α + . The percentage of CD27 - within all CD4 + T-cell populations analyzed was significantly higher on active TB compared to LTBI after PPD or ESAT-6/CFP-10 stimulation. As previously reported, a ratio based on the CD27 median fluorescence intensity (MFI) was also explored (MFI of CD27 in CD4 + T-cells over MFI of CD27 in IFN-γ + CD4 + T-cells), being significantly increased during disease ( p < 0.0001 after PPD or ESAT-6/CFP-10 stimulation). This ratio was also assessed on the other CD4 + T-cells functional profiles after specific stimulation, being significantly associated with active TB. Highest diagnostic accuracies for active TB (AUC ≥ 0.91) were achieved for: (i) CD27 within IFN-γ + TNF-α + CD4 + T-cells in response to ESAT-6/CFP-10, (ii) CD27 and CCR4 markers together within IFN-γ + CD4 + T-cells in response to PPD, and (iii) CD27 MFI ratio performed on IFN-γ + TNF-α + CD4 + T-cells after ESAT-6/CFP-10 stimulation. The lowest diagnostic accuracy was observed when CCR4 marker was evaluated alone (AUC ≤ 0.77). CD27 and CCR4 expression detection could serve as a good method for immunodiagnosis. Moreover, the immunological characterization of markers/subset populations could be a promising tool for understanding the biological basis of the disease.

Background: To evaluate the accuracy of systematic mediastinal staging by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) (sampling of all visible nodes measuring ≥5 mm from stations N3 to N1 regardless of their positron emission tomography/computed tomography [PET/CT] features) and compare this staging approach with targeted EBUS-TBNA staging (sampling only 18F-fluorodeoxyglucose [FDG]-avid nodes) in patients with N2 non-small cell lung cancer on PET/CT., Methods: Retrospective study of 107 patients who underwent systematic EBUS-TBNA mediastinal staging. The results were compared with those of a hypothetical scenario where only FDG-avid nodes on PET/CT would be sampled., Results: Systematic EBUS-TBNA sampling demonstrated N3 disease in 3 patients, N2 disease in 60 (42 single-station or N2a, 18 multiple-station or N2b) and N0/N1 disease in 44. Of these 44, 7 underwent mediastinoscopy, which did not show mediastinal disease; 6 of the 7 proceeded to lung resection, which also showed no mediastinal disease. Thirty-four N0/N1 patients after EBUS-TBNA underwent lung resection directly: N0/N1 was found in 30 and N2 in 4 (1 N2b with a PET/CT showing N2a disease, 3 N2a). Sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy of systematic EBUS-TBNA were 94%, 100%, 90%, 100% and 96%, respectively. Compared with targeted EBUS-TBNA, systematic EBUS-TBNA sampling provided additional important clinical information in 14 cases (13%): 3 N3 cases would have passed unnoticed, and 11 N2b cases would have been staged as N2a., Conclusions: In clinical practice, systematic sampling of the mediastinum by EBUS-TBNA, regardless of PET/CT features, is to be recommended over targeted sampling., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: The relationship between environmental factors and the exacerbation of respiratory diseases has been widely studied. However, there are no studies examining the relationship between these factors and bronchiectasis exacerbations. Our objective was to analyse the association between various environmental factors and hospitalisation for bronchiectasis., Material and Methods: This was a retrospective observational study conducted at two hospitals in Badalona (Barcelona). The number of hospital admissions for exacerbation of bronchiectasis between 2007 and 2015 was obtained. Through multiple regression we analysed the relationship between the number of exacerbations and mean monthly values of temperature, SO 2 , NO, NO 2 , O 3 and CO., Results: Temperature, SO 2 , NO, NO 2 , O 3 and CO were significantly associated with an increase in admissions due to exacerbation of bronchiectasis. By controlling the effect of temperature on the pollution variables, only SO 2 maintained statistical significance (P=.008)., Conclusion: We have detected an increase in hospital admissions for exacerbation of bronchiectasis with increases in the atmospheric concentration of SO 2 and the decrease in temperature. Prospective studies with different geographical locations to confirm these results are needed., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Introduction: Air pollution has been widely associated with respiratory diseases. Nevertheless, the association between air pollution and exacerbations of bronchiectasis has been less studied., Objective: To analyze the effect of air pollution on exacerbations of bronchiectasis., Methods: This was a retrospective observational study conducted in Badalona. The number of daily hospital admissions and emergency room visits related to exacerbation of bronchiectasis (ICD-9 code 494.1) between 2008 and 2016 was obtained. We used simple Poisson regressions to test the effects of daily mean temperature, SO2, NO2, CO, and PM10 levels on bronchiectasis-related emergencies and hospitalizations on the same day and 1-4 days after. All p values were corrected for multiple comparisons., Results: SO2 was significantly associated with an increase in the number of hospitalizations (lags 0, 1, 2, and 3). None of these associations remained significant after correcting for multiple comparisons. The number of emergency room visits was associated with higher levels of SO2 (lags 0-4). After correcting for multiple comparisons, the association between emergency room visits and SO2 levels was statistically significant for lag 0 (p = 0.043), lag 1 (p = 0.018), and lag 3 (p = 0.050)., Conclusions: The number of emergency room visits for exacerbation of bronchiectasis is associated with higher levels of SO2., (© 2018 S. Karger AG, Basel.)

In the last 2 decades, drug-resistant tuberculosis has become a threat and a challenge to worldwide public health. The diagnosis and treatment of these forms of tuberculosis are much more complex and prognosis clearly worsens as the resistance pattern intensifies. Nevertheless, it is important to remember that with the appropriatesystematic clinical management, most of these patients can be cured. These guidelines itemize the basis for the diagnosis and treatment of all tuberculosis patients, from those infected by strains that are sensitive to all drugs, to those who are extensively drug-resistant. Specific recommendations are given forall cases. The current and future role of new molecular methods for detecting resistance, shorter multi-drug-resistant tuberculosis regimens, and new drugs with activity against Mycobacterium tuberculosis are also addressed., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Information on the association of lung cancer (LC) and combined pulmonary fibrosis and emphysema (CPFE) is limited and derived almost exclusively from series in Asian populations. The main objective of the study was to assess the impact of LC on survival in CPFE patients and in patients with idiopathic pulmonary fibrosis (IPF)., Methods: A retrospective study was performed with data from patients with CFPE and IPF diagnosed in our hospital over a period of 5 years., Results: Sixty-six patients were included, 29 with CPFE and 37 with IPF. Nine had a diagnosis of LC (6 with CPFE and 3 with IPF). Six patients (67%) received palliative treatment even though 3 of them were diagnosed atstage i-ii. Overall mortality did not differ significantly between groups; however, in patients with LC, survival was significantly lower compared to those without LC (P=.044). The most frequent cause of death was respiratory failure secondary to pulmonary fibrosis exacerbation (44%). In a multivariate analysis, the odds ratio of death among patients with LC compared to patients without LC was 6.20 (P=.037, 95% confidence interval: 1.11 to 34.48)., Conclusions: Lung cancer reduces survival in both entities. The diagnostic and therapeutic management of LC is hampered by the increased risk of complications after any treatment modality, even after palliative treatment., (Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The present study sought to evaluate the usefulness of EBUS-TBNA in the diagnosis of locoregional recurrence of lung cancer in a cohort of lung cancer patients who were previously treated surgically, and describe our initial experience of EUS-B-FNA in this clinical scenario., Methods: We retrospectively studied the clinical records of all patients with a previous surgically-treated lung cancer who were referred to our bronchoscopy unit after suspicion of locoregional recurrence. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of EBUS-TBNA for the diagnosis of locoregional recurrence were evaluated., Results: Seventy-three patients were included. EBUS-TBNA confirmed malignancy in 40 patients: 34 confirmed to have locoregional recurrence, six had metachronous tumours. Of the 33 patients with non-malignant EBUS-TBNA; 2 had specific non-malignant diseases, 26 underwent radiological follow up and 5 patients underwent surgery. Of the 26 patients who had radiological follow up; 18 remained stable, three presented thoracic radiological progression and 5 presented extrathoracic progression. Of the 5 patients who underwent surgery; 3 had metachronous tumours, one confirmed to be a true negative and one presented nodal invasion. Seven patients underwent EUS-B-FNA, four of them confirmed to have recurrence. The sensitivity, specificity, NPV, PPV and overall accuracy of EBUS-TBNA for the diagnosis of locoregional recurrence were 80.9, 100, 69.2, 100 and 86.6% respectively., Conclusions: EBUS-TBNA is an accurate procedure for the diagnosis of locoregional recurrence of surgically-treated lung cancer. EUS-B-FNA combined with EBUS-TBNA broads the diagnostic yield of EBUS-TBNA alone.

Background: A thorough analysis of continuous adventitious sounds (CAS) can provide distinct and complementary information about bronchodilator response (BDR), beyond that provided by spirometry. Nevertheless, previous approaches to CAS analysis were limited by certain methodology issues. The aim of this study is to propose a new integrated approach to CAS analysis that contributes to improving the assessment of BDR in clinical practice for asthma patients., Methods: Respiratory sounds and flow were recorded in 25 subjects, including 7 asthma patients with positive BDR (BDR+), assessed by spirometry, 13 asthma patients with negative BDR (BDR-), and 5 controls. A total of 5149 acoustic components were characterized using the Hilbert spectrum, and used to train and validate a support vector machine classifier, which distinguished acoustic components corresponding to CAS from those corresponding to other sounds. Once the method was validated, BDR was assessed in all participants by CAS analysis, and compared to BDR assessed by spirometry., Results: BDR+ patients had a homogenous high change in the number of CAS after bronchodilation, which agreed with the positive BDR by spirometry, indicating high reversibility of airway obstruction. Nevertheless, we also found an appreciable change in the number of CAS in many BDR- patients, revealing alterations in airway obstruction that were not detected by spirometry. We propose a categorization for the change in the number of CAS, which allowed us to stratify BDR- patients into three consistent groups. From the 13 BDR- patients, 6 had a high response, similar to BDR+ patients, 4 had a noteworthy medium response, and 1 had a low response., Conclusions: In this study, a new non-invasive and integrated approach to CAS analysis is proposed as a high-sensitive tool for assessing BDR in terms of acoustic parameters which, together with spirometry parameters, contribute to improving the stratification of BDR levels in patients with obstructive pulmonary diseases., Competing Interests: The authors have declared that no competing interests exist.